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Relationship between Blood Pressure and Incident Cardiovascular Disease : Linear and Nonlinear Mendelian Randomization Analyses

Malik, Rainer ; Georgakis, Marios K. ; Vujkovic, Marijana ; Damrauer, Scott M. ; Elliott, Paul ; Karhunen, Ville ; Giontella, Alice LU orcid ; Fava, Cristiano LU ; Hellwege, Jacklyn N. and Shuey, Megan M. , et al. (2021) In Hypertension 77(6). p.2004-2013
Abstract

Observational studies exploring whether there is a nonlinear effect of blood pressure on cardiovascular disease (CVD) risk are hindered by confounding. This limitation can be overcome by leveraging randomly allocated genetic variants in nonlinear Mendelian randomization analyses. Based on their association with blood pressure traits in a genome-wide association study of 299 024 European ancestry individuals, we selected 253 genetic variants to proxy the effect of modifying systolic and diastolic blood pressure. Considering the outcomes of incident coronary artery disease, stroke and the combined outcome of CVD, linear and nonlinear Mendelian randomization analyses were performed on 255 714 European ancestry participants without a... (More)

Observational studies exploring whether there is a nonlinear effect of blood pressure on cardiovascular disease (CVD) risk are hindered by confounding. This limitation can be overcome by leveraging randomly allocated genetic variants in nonlinear Mendelian randomization analyses. Based on their association with blood pressure traits in a genome-wide association study of 299 024 European ancestry individuals, we selected 253 genetic variants to proxy the effect of modifying systolic and diastolic blood pressure. Considering the outcomes of incident coronary artery disease, stroke and the combined outcome of CVD, linear and nonlinear Mendelian randomization analyses were performed on 255 714 European ancestry participants without a history of CVD or antihypertensive medication use. There was no evidence favoring nonlinear relationships of genetically proxied systolic and diastolic blood pressure with the cardiovascular outcomes over linear relationships. For every 10-mm Hg increase in genetically proxied systolic blood pressure, risk of incident CVD increased by 49% (hazard ratio, 1.49 [95% CI, 1.38-1.61]), with similar estimates obtained for coronary artery disease (hazard ratio, 1.50 [95% CI, 1.38-1.63]) and stroke (hazard ratio, 1.44 [95% CI, 1.22-1.70]). Genetically proxied blood pressure had a similar relationship with CVD in men and women. These findings provide evidence to support that even for individuals who do not have elevated blood pressure, public health interventions achieving persistent blood pressure reduction will be of considerable benefit in the primary prevention of CVD.

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organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
blood pressure, coronary artery disease, hypertension, primary prevention, stroke
in
Hypertension
volume
77
issue
6
pages
10 pages
publisher
Lippincott Williams & Wilkins
external identifiers
  • scopus:85105789406
  • pmid:33813844
ISSN
0194-911X
DOI
10.1161/HYPERTENSIONAHA.120.16534
language
English
LU publication?
yes
id
4b010652-b5dc-483d-81a6-28f7acdc5a51
date added to LUP
2021-05-28 08:29:21
date last changed
2024-04-20 06:35:18
@article{4b010652-b5dc-483d-81a6-28f7acdc5a51,
  abstract     = {{<p>Observational studies exploring whether there is a nonlinear effect of blood pressure on cardiovascular disease (CVD) risk are hindered by confounding. This limitation can be overcome by leveraging randomly allocated genetic variants in nonlinear Mendelian randomization analyses. Based on their association with blood pressure traits in a genome-wide association study of 299 024 European ancestry individuals, we selected 253 genetic variants to proxy the effect of modifying systolic and diastolic blood pressure. Considering the outcomes of incident coronary artery disease, stroke and the combined outcome of CVD, linear and nonlinear Mendelian randomization analyses were performed on 255 714 European ancestry participants without a history of CVD or antihypertensive medication use. There was no evidence favoring nonlinear relationships of genetically proxied systolic and diastolic blood pressure with the cardiovascular outcomes over linear relationships. For every 10-mm Hg increase in genetically proxied systolic blood pressure, risk of incident CVD increased by 49% (hazard ratio, 1.49 [95% CI, 1.38-1.61]), with similar estimates obtained for coronary artery disease (hazard ratio, 1.50 [95% CI, 1.38-1.63]) and stroke (hazard ratio, 1.44 [95% CI, 1.22-1.70]). Genetically proxied blood pressure had a similar relationship with CVD in men and women. These findings provide evidence to support that even for individuals who do not have elevated blood pressure, public health interventions achieving persistent blood pressure reduction will be of considerable benefit in the primary prevention of CVD.</p>}},
  author       = {{Malik, Rainer and Georgakis, Marios K. and Vujkovic, Marijana and Damrauer, Scott M. and Elliott, Paul and Karhunen, Ville and Giontella, Alice and Fava, Cristiano and Hellwege, Jacklyn N. and Shuey, Megan M. and Edwards, Todd L. and Rogne, Tormod and Åsvold, Bjørn O. and Brumpton, Ben M. and Burgess, Stephen and Dichgans, Martin and Gill, Dipender}},
  issn         = {{0194-911X}},
  keywords     = {{blood pressure; coronary artery disease; hypertension; primary prevention; stroke}},
  language     = {{eng}},
  number       = {{6}},
  pages        = {{2004--2013}},
  publisher    = {{Lippincott Williams & Wilkins}},
  series       = {{Hypertension}},
  title        = {{Relationship between Blood Pressure and Incident Cardiovascular Disease : Linear and Nonlinear Mendelian Randomization Analyses}},
  url          = {{http://dx.doi.org/10.1161/HYPERTENSIONAHA.120.16534}},
  doi          = {{10.1161/HYPERTENSIONAHA.120.16534}},
  volume       = {{77}},
  year         = {{2021}},
}